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PubMed2002

Working memory neurons in pigeons.

Working memory, the ability to temporarily store and manipulate currently relevant information, is required for most cognitive faculties. In humans and other mammals, the prefrontal cortex (PFC) provides the underlying neural network for these processes. Within the PFC, working memory neurons display sustained elevated activity while holding active an internal representation of the relevant stimulus during its physical absence or retaining a motor plan for the forthcoming response. Working memory, however, is not a hallmark of higher vertebrates endowed with a neocortex. Birds also master complex cognitive problems invoking working memory, but they lack a laminated neocortex. Behavioral studies in pigeons show that the neostriatum caudolaterale (NCL) plays a central role in executive functions, such as working memory and response control. For neurons in the NCL of pigeons, we show activity changes during the delay of a working memory task, which were similar to those observed in PFC neurons and were related to the successful holding of information in memory and to the subsequent behavior. Thus, although the anatomical and morphological structure of the neuronal substrate in birds is radically different from the mammalian neocortical architecture, the neuronal mechanisms evolved to master equivalent cognitive demands seem to be very similar.

Analysis of Variance↗
PubMed2000

TMT, a predator odor, elevates mesoprefrontal dopamine metabolic activity and disrupts short-term working memory in the rat.

Working memory has been proposed to require the proper functioning of the medial prefrontal cortex and its dopaminergic innervation. The dopaminergic input to the medial prefrontal cortex has been demonstrated to be sensitive to physical and psychological stress. In this report, we demonstrate that a brief exposure to 2, 5-dihydro-2,4,5-trimethylthiazoline (TMT), an odor derived from a predator of the rat, the fox, resulted in elevated dopamine metabolism in the medial prefrontal cortex and elevated serum corticosterone. We tested the effects of this olfactory stress on working memory using a spontaneous, delayed, non-matching-to-sample task using object recognition methods. Rats were exposed to one set of objects and, after a delay of 1, 15 or 60 min, later demonstrated a robust working memory of the familiar object compared to a novel object. When rats were exposed to TMT during the 15-min delay, working memory was disrupted without altering exploratory behavior. We conclude from these studies that (1) TMT selectively activates mesoprefrontal dopamine neurons, (2) TMT exposure can disrupt working memory and (3) this disruption in working memory is not due to an overall suppression of exploratory behavior but may involve altered mesoprefrontal dopaminergic activity.

Animals↗
PubMed2007

Temporal properties of posterior parietal neuron discharges during working memory and passive viewing.

Working memory is mediated by the discharges of neurons in a distributed network of brain areas. It was recently suggested that enhanced rhythmicity in neuronal activity may be critical for sustaining remembered information. To test whether working memory is characterized by unique temporal discharge patterns, we analyzed the autocorrelograms and power spectra of spike trains recorded from the posterior parietal cortex of monkeys performing a visuospatial working-memory task. We compared the intervals of active memory maintenance and fixation and repeated the same analysis in spike trains from monkeys never trained to perform any kind of memory task. The most salient effect we observed was a decrease of power in the 5- to 10-Hz frequency range during the presentation of visual stimuli. This pattern was observed both in the working-memory condition and the control condition, although it was more prominent in the former, where it persisted after cue presentation when the monkeys actively remembered the spatial location of the stimulus. Low-frequency power suppression resulted from relative refractory periods that were significantly longer in the working-memory condition and presumably emerged from local-circuit inhibition. We also detected a spectral peak in the 15- to 20-Hz range, although this was more prominent during fixation than during the stimulus and working-memory periods. Our results are in line with previous reports in prefrontal cortex and indicate that unique temporal patterns of single-neuron firing characterize persistent delay activity, although these do not involve the appearance of enhanced oscillations.

Action Potentials↗
PubMed2003

A within-subjects, within-task demonstration of intact spatial reference memory and impaired spatial working memory in glutamate receptor-A-deficient mice.

Gene-targeted mice lacking the AMPA receptor subunit glutamate receptor-A (GluRA) (GluR1) and wild-type controls were compared on a radial-maze task in which the same three of six arms were always baited, but in which the rewards of milk were not replaced within a trial. This procedure allowed not only a within-subjects but also a within-trials assessment of both spatial working memory (WM) and reference memory (RM) in GluRA-/- mice, using identical spatial cues. In experiment 1, the GluRA-/- mice made more WM and RM errors during task acquisition. However, separate groups of GluRA-/- and wild-type mice (experiment 2) acquired a purely RM version of the task at a similar rate, using a paradigm with which it was not possible to make WM errors (doors prevented mice from re-entering an arm that they had already visited on that trial). In contrast, mice with hippocampal lesions were dramatically impaired. These results are consistent with the possibility that the WM impairment in the GluRA-/- mice during experiment 1 produced interference that disrupted RM acquisition. A WM component was therefore introduced after RM acquisition in experiment 2 (i.e., the mice were no longer prevented from re-entering a previously visited arm). The GluRA-/- mice now made considerably more WM errors than did wild-type mice, but simultaneously, RM was only mildly and transiently impaired. These experiments provide additional evidence of a selective spatial WM deficit coexisting with intact spatial RM acquisition in GluRA-/- mice, suggesting that different neuronal mechanisms within the hippocampus may support these different kinds of information processing.

Animals↗
PubMed2004

Visual search is slowed when visuospatial working memory is occupied.

Visual working memory plays a central role in most models of visual search. However, a recent study showed that search efficiency was not impaired when working memory was filled to capacity by a concurrent object memory task (Woodman, Vogel, & Luck, 2001). Objects and locations may be stored in separate working memory subsystems, and it is plausible that visual search relies on the spatial subsystem, but not on the object subsystem. In the present study, we sought to determine whether maintaining spatial information in visual working memory impairs the efficiency of a concurrent visual search task. Visual search efficiency and spatial memory accuracy were both impaired when the search and the memory tasks were performed concurrently, as compared with when the tasks were performed separately. These findings suggest that common mechanisms are used to process information during difficult visual search tasks and to maintain spatial information in working memory.

Fixation, Ocular↗
PubMedDate not supplied

[Working memory: neuropsychological and neurobiological issues].

Working memory denotes an ability to remember information for a short-time and to manipulate it. The memory allows including correct information depending on the situation, to keep the information on present activities for a while and enables changing the reaction according to new criteria. The relation between working memory and efficiency of complex cognitive processes and also with the control of emotional processes, plasticity of behaviour and consciousness was demonstrated. Working memory is connected with the activity of the dorsolateral prefrontal cortex of the brain. Recently, it has been shown, that working memory disturbances play an important role in the aetiopathogenesis of psychiatric disturbances such as schizophrenia, bipolar affective disorder or obsessive-compulsive disorder. Working memory disturbances are also shown in a proportion of healthy first-degree relatives of patients with schizophrenia or bipolar disorders. Working memory disturbances are presently regarded as a cognitive endophenotypic marker of vulnerability to these illnesses. In recent years, an association between working memory abilities and activity of different neurotransmitters, especially with the dopaminergic system in the brain, has been shown. Molecular genetic studies show an association between working memory abilities and polymorphism of the dopaminergic system genes in schizophrenia and polymorphism of BDNF gene in bipolar affective disorders. So far not much data about the genetics of working memory in healthy subjects has been gathered. Currently in Poland such research is carried on in the Clinical Neuropsychology Unit Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz in cooperation with the Department of Adult Psychiatry and Laboratory of Psychiatric Genetics University of Medical Sciences in Poznań.

Bipolar Disorder↗
PubMed2001

Lack of effect of moderate Purkinje cell loss on working memory.

192 immunoglobulin G-saporin (192-sap) is an immunotoxin which targets the cholinergic basal forebrain after injection into either the ventricular system or the parenchyma of the rat brain. When injected by the i.c.v. route, 192-sap kills some cerebellar Purkinje cells in addition to its more extensive killing of the cholinergic basal forebrain. Behaviorally, i.c.v. injections of 192-sap result in impaired performance in a variety of experimental paradigms of learning and memory including a working memory task in the radial maze. The current study examined the contribution, if any, of immunotoxin-induced Purkinje cell loss to impaired performance in the radial maze. To meet this aim, we used i.c.v. injection of another immunotoxin, OX7-saporin (OX7-sap), at a dose that produced Purkinje cell loss of similar extent to that produced by i.c.v. 192-sap. We then compared these OX7-sap-injected rats with 192-sap-injected rats in a radial maze working memory task. We found a working memory impairment only in the 192-sap-injected rats. These data show that moderate Purkinje cell loss alone is insufficient to impair working memory. Furthermore, the data are consistent with the idea that the working memory deficit observed in 192-sap-injected animals is likely due to lesioning of the cholinergic basal forebrain.

Animals↗
PubMed1998

Selective attention in schizophrenia: relationship to verbal working memory.

In previous work using the Stroop task to examine cognitive function in schizophrenia, we have suggested that reaction time (RT) facilitation and error interference should be more sensitive measures of cognitive function than RT interference. We examined this hypothesis in 36 DSM-IV schizophrenia and schizoaffective patients, who performed both the Stroop and the Speaking Span, a measure of verbal working memory. The results supported our hypotheses, demonstrating that RT facilitation and error interference were associated more strongly with working memory performance than RT interference. The robust correlations between these measures of selective attention and Speaking Span performance has implications for understanding the nature and selectivity of cognitive dysfunction in schizophrenia. We present several different hypotheses that may explain this relationship, including: (1) a generalized deficit; (2) a common cognitive disturbance; and (3) a common neurobiological dysfunction.

Adult↗
PubMed2006

Executive and visuospatial sketchpad resources in euthymic bipolar disorder: Implications for visuospatial working memory architecture.

Visuospatial working memory theory is used to interpret the cognitive impairment in euthymic bipolar disorder. Such patients show deficits in the Corsi Blocks Test (CBT) and executive control. To understand these deficits, 20 euthymic bipolar patients and controls were administered the CBT, Visual Patterns Test (VPT), and a new visual memory task designed to make minimal demands on executive resources. Initial analyses validated the visual memory task and implicated executive involvement in the CBT and VPT. Subsequent analyses on a number of tests confirmed CBT and executive deficits while performance was normal on the VPT and visual memory test. ANCOVA indicated that impaired executive function underpinned patients' CBT performance. Implications for the interface between executive and slave systems of working memory are discussed.

Adolescent↗
PubMed2002

De-coupling of cognitive performance and cerebral functional response during working memory in schizophrenia.

Working memory dysfunction is considered to be fundamental to the cognitive and clinical features evident in schizophrenia. Functional neuroimaging studies have begun to elucidate the neurobiological basis of such deficits, however, interpretation of these studies may be confounded by performance impairment, when the cognitive load exceeds the limited response capacity of patients with schizophrenia. In this study, patients were pre-selected on the basis of intact performance on a relatively low-load verbal working memory task, in order to mitigate against performance confounds. Subjects included 20 right-handed male subjects with chronic schizophrenia, and 20 right-handed, age-matched, male healthy controls, without personal or familial psychiatric history. All subjects underwent fMRI scanning whilst performing a verbal n-back task. There were no significant between-group differences in target identification; the patient group showed a significantly increased mean response latency. Both groups demonstrated robust fronto-parietal activation. In the control subjects, the power of functional response was positively correlated with reaction time in bilateral posterior parietal cortex, however, this coupling of behavioural performance and cerebral response was not evident in the patients. This deficit, apparent within the performance capacity of the patients, may represent a fundamental abnormality in schizophrenia, and may compromise performance at higher cognitive loads.

Adult↗
PubMed2005

Fronto-parietal EEG coherence in theta and upper alpha reflect central executive functions of working memory.

For human working memory the neural correlates of the phonological loop and the visuospatial sketch pad are well explored. In contrast, less is known about central executive processes. Neuroimaging studies suggest that central executive processes are related to a complex fronto-parietal network. In the present study we investigate the question whether varying demands on central executive processes are reflected by differences in coherent activity between and within a fronto-parietal network. We calculated coherence during a visuospatial working memory task. Under an easy executive condition subjects had to mentally imagine previously studied abstract patterns, whereas in the difficult condition, subjects had to mentally manipulate these patterns. The results indicate the involvement of prefrontal areas in executive functions reflected by a decrease of anterior upper alpha short-range connectivity and a parallel increase of fronto-parietal long-range coherence mirroring activation of a fronto-parietal network.

Adult↗
PubMed1998

Taking a computational approach to aging: the SPAN theory of working memory.

The decline of working memory capacity associated with normal adult aging is well-known. What is less well established is the cause of this decline. One prominent proposal is that working memory decline is caused by a reduction in basic information-processing speed, but this account has lacked a demonstration that general slowing is computationally sufficient to produce a decrease in working memory capacity. This article presents a production system theory of working memory (SPAN) based on established mechanisms: slowing, decay, and displacement. Models of 2 tasks--digit symbol and computation span--which have been prominent in research on slowing, are presented in detail. These models demonstrate that slowing is sufficient to produce differences in these tasks, and they provide a quantitative match to observed young-old differences as well. This advance for slowing theory also demonstrates the viability of computational tools in aging research.

Adult↗
PubMed2000

Working memory structure and intellectual disability.

The working memory of people with intellectual disability has been found to generally lag behind their mental age. However, studies concerning the structure of working memory or its connections to other cognitive functions are rare. The present study employs a versatile battery of tests for the evaluation of working memory structure in adults with intellectual disability of unknown aetiology. In addition, connections between working memory and cognitive skills valid for everyday functioning are evaluated. Working memory performance in the study participants was found to stem from two distinct components which could be regarded to represent phonological and general working memory. General working memory was closely related to intelligence, whereas phonological working memory was not. The subjects in the study group differed in their working memory profiles. These distinct profiles were significantly related to academic skills (e.g. reading, writing and mathematics) and sentence comprehension because the profile of the working memory predicted these abilities even when the intelligence and educational background of the participants was taken into consideration.

Achievement↗
PubMed2006

Delayed-execute prospective memory performance: the effects of age and working memory.

This study follows the novel delayed-execute prospective memory paradigm, which involves briefly delaying the execution of an intended action, a task that has been shown to produce substantial age effects. During the ongoing task, sentences were presented, and participants had to answer reading-comprehension questions and general knowledge questions. In the prospective memory task, the participant was to press a key after the presentation of a specific cue in the sentences-but not before a subsequent phase of the ongoing task was reached. In contrast to previous studies using older participants taken from very broadly defined age ranges, this study examines development of delayed-execute prospective memory more precisely by examining a total of 4 age groups: a younger age group (age range = 22-31; n = 27), a young-old age group (age range = 60-69; n = 34), a middle-old age group (age range = 70-79; n = 31), and an old-old age group (age range = 80-91; n = 35). This study investigates the dependence of (age-related) delayed-execute prospective memory performance on working memory capacity by disrupting the phonological loop during the delay period as well as its dependence on neuropsychological processes such as inhibitory control and processing speed. The results show that (a) delayed-execute prospective memory particularly declines within the group of older participants, (b) delayed-execute prospective memory is diminished when working memory load is high during the delay period, and (c) age-related performance in delayed-execute prospective memory may be mediated by inhibitory control. The findings are discussed in the context of the frontal lobe hypothesis of cognitive aging.

Adult↗
PubMed1999

Hemispheric asymmetry of spatial working memory deficit in schizophrenia.

Spatial working memory function was assessed in schizophrenia patients, hypothetically 'psychosis-prone' individuals who report unusual perceptual experiences and normal control subjects with an oculomotor delayed response task. Past studies point to the important role of dorsolateral prefrontal system in spatial working memory deficits of schizophrenia patients. In order to better understand the processes precipitating in working memory deficit, two types of working memory errors were examined: never-corrected vs. immediately-corrected errors. In schizophrenia patients, the loss of spatial representation in working memory, as captured by the presence of never-corrected errors, was much more severe when the target was presented in the right visual hemifield than when the target was presented in the left visual field. The same pattern was observed in healthy, psychometrically ascertained 'psychosis-prone' subjects. Therefore, the observed asymmetry of spatial working memory deficit seems unlikely to be a mere side-effect of medication or hospitalization. Normal control subjects did not show hemispheric asymmetry in error patterns. These results suggest that the loss of spatial representation during a delay period may be more severe in the left hemisphere in patients with schizophrenia and in 'psychosis-prone' individuals.

Adult↗
PubMed2007

The nature of individual differences in working memory capacity: active maintenance in primary memory and controlled search from secondary memory.

Studies examining individual differences in working memory capacity have suggested that individuals with low working memory capacities demonstrate impaired performance on a variety of attention and memory tasks compared with individuals with high working memory capacities. This working memory limitation can be conceived of as arising from 2 components: a dynamic attention component (primary memory) and a probabilistic cue-dependent search component (secondary memory). This framework is used to examine previous individual differences studies of working memory capacity, and new evidence is examined on the basis of predictions of the framework to performance on immediate free recall. It is suggested that individual differences in working memory capacity are partially due to the ability to maintain information accessible in primary memory and the ability to search for information from secondary memory.

Attention↗
PubMed2001

Working memory interference control deficit in children referred by teachers for ADHD symptoms.

It has been hypothesised that children with Attention Deficit/Hyperactivity Disorder (ADHD) present memory problems, including working memory deficits. This research is aimed at finding clearer evidence of a working memory deficit in these children. In the first study 22 children that had been referred by teachers as having ADHD symptoms were compared with a control group. Their performance on a listening span test, drawn up by De Beni, Palladino, Pazzaglia, and Cornoldi (1998), was investigated. In this task the subjects were asked to select the names of animals in word strings and to remember the last word in each string. In a second study, 34 children with ADHD symptoms and 50 control children were presented with a visuospatial working memory task mirroring the verbal task used in Study 1. In both studies, the children with ADHD symptoms had difficulty in remembering the last item in the string and had a higher number of intrusions when memorising items that were not in the final position. The results were interpreted that children with ADHD symptoms have working memory problems because they are not capable of suppressing information that initially has to be processed, and subsequently excluded from memory. This particular difficulty can be interpreted as an inhibitory processing deficit. The implications of the results in understanding learning difficulties in children with ADHD are discussed.

Attention↗
PubMed2003

Developmental D-methamphetamine treatment selectively induces spatial navigation impairments in reference memory in the Morris water maze while sparing working memory.

In previous studies, we have shown that P11-20 treatment with D-methamphetamine (MA) (10 mg/kg x 4/day at 2-h intervals) induces impairments in spatial learning and memory in the Morris water maze after the offspring reach adulthood. Using a split-litter, multiple dose, design (0, 5, 10, and 15 mg/kg MA administered s.c. 4/day at 2-h intervals), the spatial learning effect was further explored with a multiple shifted platform (reversal), reference memory-based procedure and a working memory procedure. Prior to spatial learning, animals were first tested for swimming ability (in a straight swimming channel), sequential learning (in the Cincinnati multiple-T water maze), and proximal cue learning (in the Morris water maze). Rats were then assessed in the hidden platform, reference memory-based spatial version of the Morris maze for acquisition and on five subsequent phases in which the platform was moved to new locations. After the reference memory-based, fixed platform position learning phases, animals were tested in the trial-dependent, matching-to-sample, working memory version of the Morris maze. No group differences were found in straight channel, sequential maze, or cued Morris maze performance. By contrast, all MA groups were impaired in spatial learning during acquisition, multiple shift, and shifted with a reduced platform phases of reference memory-based learning. In addition, MA animals were impaired on memory (probe) trials during the acquisition and shifted with a reduced platform phases of learning. No effects on trial-dependent, matching-to-sample, working memory were found. The findings demonstrate that neonatal treatment with MA induces a selective impairment of reference memory-based spatial learning while sparing sequential, cued, and working memory-based learning.

Animals↗